Lopez Laboratory

Virus-Host Interactions and Innate Immunity

Our body, as well as that of all other animals, is equipped with a complex defense system that protects us from microbes that cause disease. Our laboratory studies the signals that turn on and regulate this defense system –the immune system- when we are infected with common viruses, such as the influenza virus or the respiratory syncytial virus. These viruses can cause or exacerbate chronic lung diseases, such as asthma, and can be fatal in some patients.

The immune response that prevents the virus from growing to dangerous levels and causing disease can be very damaging to our own body if turned on in the absence of real threat from disease-causing microbes; thus, the immune response it is tightly regulated and is only active upon recognition of specific signals from the invading pathogens by specialized cellular proteins.

By identifying the viral and cellular molecules involved in initiating the immune response during infection and by elucidating how our body protects itself from the ammunitions of the immune system, we hope to contribute to the development of better antiviral treatments and vaccines to protect humans and other animals from these infections.

Ongoing projects

Our laboratory focuses on the study of the innate immune response to respiratory viruses. We are particularly interested in understanding the early events of the virus-host interaction that determine the quality of the antiviral response and the clinical outcome of the infection. We hope to gather knowledge that will lead to the development of better antiviral therapies and vaccines. We are interested in the following specific areas:

Identification and characterization of viral features and host molecular mechanisms that determine the onset and quality of the antiviral immune response.

Characterization of host mechanisms that regulate the antiviral immune response ensuring clearance of the virus while minimizing damage of the host tissue.

Are defective viral genomes the ultimate trigger for antiviral immunity?

We have described a critical role for defective viral genomes (DVGs), which were until recently considered an epiphenomenon of in vitro virus replication, as primary stimuli for the activation of the antiviral response, both in vitro and in vivo. DVGs are generated by a large number of animal and plant viruses, but their role during the virus-host cycle remained speculative. We recently demonstrated that DVGs arise naturally during mouse infection with SeV or with mouse-adapted influenza virus and provide primary danger signals for the initiation of the antiviral response in the lung. We are interested in identifying viral features that confer the potent immunostimulatory activity to DVGs and to harness these motifs for the development of novel adjuvants. We are also interested in characterizing the host pathways involved in the response to DVGs in order to identify potential targets for antiviral therapy. Moreover, we are investigating the role of DVGs in determining the antiviral response during respiratory infections in the human lung in order to establish the role of DVGs in respiratory virus pathogenesis in humans.

Systemic regulation of the lung antiviral response

Upon viral recognition and sensing of the infecting virus, infected cells produce cytokines and chemokines that promote the recruitment and activation of immune cells. We reported that soon after a respiratory infection, molecules produced in the infected lung are transported through the blood to signal cells located in the distal bone marrow. Cells instructed in the bone marrow by type I IFNs produced in the lung and transported to the bone marrow through the blood become resistant to virus infection and respond more efficiently to viral cues when recruited to the lung, therefore enhancing the innate immune response and facilitating the clearance of the virus. We are currently interested in characterizing other mediators of the lung-bone marrow axis and in determining their role during the initial anti-viral response. In particular, we are investigating the regulatory function of innate immune cells that massively infiltrate the lung during infection and that contribute to virus clearance while protecting the tissue for excessive damage.